title: Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).
abstract: Mutations in C-terminal titin cause autosomal dominant tibial muscular dystrophy (TMD) as reported previously. Samples from 25 new families and 25 sporadic new distal myopathy cases were screened for titin mutations. Three novel mutations were discovered in two families from Spain and two families from France. Two mutations, g.292998delT and g.293376delA lead to frameshift and premature stop codons in the second last and the last titin gene (TTN) exons, Mex5 and Mex6, respectively. The third was a nonsense mutation g.293379C>T (p.Q33396X) in Mex6. Patients with the upstream Mex5 mutation showed a more severe phenotype with earlier onset implying a genotype-phenotype correlation.
authors.affiliation: Folkhälsan Institute of Genetics, Department of Medical Genetics, University of Helsinki, Haartmaninkatu 8, Pb 63, 00014 Helsinki, Finland. peter.hackman@helsinki.fi
authors.forename: Peter
authors.initials: P
authors.lastname: Hackman
authors.forename: Sylvie
authors.initials: S
authors.lastname: Marchand
authors.forename: Jaakko
authors.initials: J
authors.lastname: Sarparanta
authors.forename: Anna
authors.initials: A
authors.lastname: Vihola
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pénisson-Besnier
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Pardal-Fernández
authors.forename: El-Hadi
authors.initials: el-H
authors.lastname: Hammouda
authors.forename: Isabelle
authors.initials: I
authors.lastname: Richard
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D018389:Codon, Nonsense; D064211:Connectin; D004252:DNA Mutational Analysis; D049310:Distal Myopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D018389:Codon, Nonsense; D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases